The aim of the investigations described in this application is to attempt to clarify some of the mechanisms responsible for the diabetic-like state associated with shock. Although some aspects of this phenomenon appear consonant with the effects of an altered glucagon: insulin ratio on various steps of glucose metabolism, other experimental facts are at variance with this explanation. Glucagon and insulin have reciprocal effects on key, rate-limiting enzymes involved in glycolysis or gluconeogenesis. Activities of glycolytic enzymes are reduced by glucagon which increases that of gluconeogenic enzymes and vice versa for insulin. By following the activities of these enzymes in different tissues of rabbits subjected to hemorrhagic shock, we hope to be able to determine whether the changes if any follow a pattern which may be ascribed to the predominant action of one or the other of these 2 hormones. In parallel experiments we plan to look at the direction of glucose flux in these tissues with the aid of changes in levels of glycolytic intermediates. We will be searching for a correlation between changes in the levels of these substrates and changes in the activities of the enzymes regulating their metabolism. The ultimate goal will be to find out whether or not changes in glucose metabolism produced by shock do or do not preclude modification of cellular utilization of glucose in a direction more favorable to cellular energy transduction; modification by such means as exogenous glucose, insulin, ATP among others.